Manganese-porphyrin reactions with lipids and lipoproteins

Manganese porphyrin complexes serve to catalytically scavenge superoxide, hydrogen peroxide, and peroxynitrite. Herein, reactions of manganese 5,10,15,20-tetrakis(N-ethylpyridinium-2-yl)porphyrin (MnTE-2-PyP5+) with lipids and lipid hydroperoxides (LOOH) are examined. In linoleic acid and human low-density lipoprotein (LDL), MnTE-2-PyP5+ promotes oxidative reactions when biological reductants are not present. By redox cycling between Mn+3 and Mn+4 forms, MnTE-2-PyP5+ initiates lipid peroxidation via decomposition of 13(S)hydroperoxyoctadecadienoic acid [13(S)HPODE], with a second-order rate constant of 8.9 × 103 M−1s−1and kcat = 0.32 s−1. Studies of LDL oxidation demonstrate that: (i) MnTE-2-PyP5+ can directly oxidize LDL, (ii) MnTE-2-PyP5+ does not inhibit Cu-induced LDL oxidation, and (iii) MnTE-2-PyP5+ plus a reductant partially inhibit lipid peroxidation. MnTE-2-PyP5+ (1–5 μM) also significantly inhibits FeCl3 plus ascorbate-induced lipid peroxidation of rat brain homogenate. In summary, MnTE-2-PyP5+ initiates membrane lipid and lipoprotein oxidation in the absence of biological reductants, while MnTE-2-PyP5+ inhibits lipid oxidation reactions initiated by other oxidants when reductants are present. It is proposed that, as the Mn+3 resting redox state of MnTE-2-PyP5+ becomes oxidized to the Mn+4 redox state, LOOH is decomposed to byproducts that propagate lipid oxidation reactions. When the manganese of MnTE-2-PyP5+ is reduced to the +2 state by biological reductants, antioxidant reactions of the metalloporphyrin are favored.